The work in this laboratory is focused on the relationships between the metabolism of bile acids and the formation of cholesterol gallstones in man. Our goal is to define how changes in hepatic synthesis, hepatic secretion, ileal absorption, and pool sizes of bile acids influence the solubility of cholestrol in bile. The abnormalities of bile acid metabolism existing in patients afflicted with cholelithiasis and those predisposed to gallstone disease (obesity, hypothyroidism, pregnancy, ileal dysfunction, users of estrogens, patients treated with clofibrate) comprise the nucleus of our project. Parallel efforts are made to learn how certain methods used in the treatment of hypercholesterolemia affect the metabolism of bile acids and of cholesterol. Furthermore, we are interested in validating basic methodology used in studies of bile acid metabolism. Our methods allow studies of the composition and hepatic secretion of biliary lipids and of the pool sizes and synthesis rates of bile acids. The rates of bile acid absorption and recycling of the bile acid pool can be derived indirectly from the measurements mentioned above. These biochemical and clinical studies will prove useful in improving our understanding of the mechanisms involved in the formation of gallstones and in developing measures for their prevention in high risk categories.